Rheumatoid arthritis and cardiovascular disease Crowson, Cynthia S., MS; Liao, Katherine P., MD, MPH; Davis, John M., MD ...
American heart journal/The American heart journal,
10/2013, Letnik:
166, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a “natural experiment” ...to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease. Methods A review of current literature on heart disease and RA was conducted. Results Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk. Conclusions Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease.
Conspectus Chirality in Nature can be found across all length scales, from the subatomic to the galactic. At the molecular scale, the spatial dissymmetry in the atomic arrangements of pairs of ...mirror-image molecules, known as enantiomers, gives rise to fascinating and often critical differences in chemical and physical properties. With increasing hierarchical complexity, protein function, cell communication, and organism health rely on enantioselective interactions between molecules with selective handedness. For example, neurodegenerative and neuropsychiatric disorders including Alzheimer’s and Parkinson’s diseases have been linked to distortion of chiral-molecular structure. Moreover, d-amino acids have become increasingly recognized as potential biomarkers, necessitating comprehensive analytical methods for diagnosis that are capable of distinguishing l- from d-forms and quantifying trace concentrations of d-amino acids. Correspondingly, many pharmaceuticals and agrochemicals consist of chiral molecules that target particular enantioselective pathways. Yet, despite the importance of molecular chirality, it remains challenging to sense and to separate chiral compounds. Chiral-optical spectroscopies are designed to analyze the purity of chiral samples, but they are often insensitive to the trace enantiomeric excess that might be present in a patient sample, such as blood, urine, or sputum, or pharmaceutical product. Similarly, existing separation schemes to enable enantiopure solutions of chiral products are inefficient or costly. Consequently, most pharmaceuticals or agrochemicals are sold as racemic mixtures, with reduced efficacy and potential deleterious impacts. Recent advances in nanophotonics lay the foundation toward highly sensitive and efficient chiral detection and separation methods. In this Account, we highlight our group’s effort to leverage nanoscale chiral light–matter interactions to detect, characterize, and separate enantiomers, potentially down to the single molecule level. Notably, certain resonant nanostructures can significantly enhance circular dichroism for improved chiral sensing and spectroscopy as well as high-yield enantioselective photochemistry. We first describe how achiral metallic and dielectric nanostructures can be utilized to increase the local optical chirality density by engineering the coupling between electric and magnetic optical resonances. While plasmonic nanoparticles locally enhance the optical chirality density, high-index dielectric nanoparticles can enable large-volume and uniform-sign enhancements in the optical chirality density. By overlapping these electric and magnetic resonances, local chiral fields can be enhanced by several orders of magnitude. We show how these design rules can enable high-yield enantioselective photochemistry and project a 2000-fold improvement in the yield of a photoionization reaction. Next, we discuss how optical forces can enable selective manipulation and separation of enantiomers. We describe the design of low-power enantioselective optical tweezers with the ability to trap sub-10 nm dielectric particles. We also characterize their chiral-optical forces with high spatial and force resolution using combined optical and atomic force microscopy. These optical tweezers exhibit an enantioselective optical force contrast exceeding 10 pN, enabling selective attraction or repulsion of enantiomers based on the illumination polarization. Finally, we discuss future challenges and opportunities spanning fundamental research to technology translation. Disease detection in the clinic as well as pharmaceutical and agrochemical industrial applications requiring large-scale, high-throughput production will gain particular benefit from the simplicity and relative low cost that nanophotonic platforms promise.
Comparative analyses of pathogen genomes provide new insights into how pathogens have evolved common and divergent virulence strategies to invade related plant species. Fusarium crown and root rots ...are important diseases of wheat and barley world-wide. In Australia, these diseases are primarily caused by the fungal pathogen Fusarium pseudograminearum. Comparative genomic analyses showed that the F. pseudograminearum genome encodes proteins that are present in other fungal pathogens of cereals but absent in non-cereal pathogens. In some cases, these cereal pathogen specific genes were also found in bacteria associated with plants. Phylogenetic analysis of selected F. pseudograminearum genes supported the hypothesis of horizontal gene transfer into diverse cereal pathogens. Two horizontally acquired genes with no previously known role in fungal pathogenesis were studied functionally via gene knockout methods and shown to significantly affect virulence of F. pseudograminearum on the cereal hosts wheat and barley. Our results indicate using comparative genomics to identify genes specific to pathogens of related hosts reveals novel virulence genes and illustrates the importance of horizontal gene transfer in the evolution of plant infecting fungal pathogens.
Objective
Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine whether FSE produces acute ...hippocampal injury that evolves to HS.
Methods
FEBSTAT and 2 affiliated studies prospectively recruited 226 children aged 1 month to 6 years with FSE and controls with simple febrile seizures. All had acute magnetic resonance imaging (MRI), and follow‐up MRI was obtained approximately 1 year later in the majority. Visual interpretation by 2 neuroradiologists informed only of subject age was augmented by hippocampal volumetrics, analysis of the intrahippocampal distribution of T2 signal, and apparent diffusion coefficients.
Results
Hippocampal T2 hyperintensity, maximum in Sommer's sector, occurred acutely after FSE in 22 of 226 children in association with increased volume. Follow‐up MRI obtained on 14 of the 22 with acute T2 hyperintensity showed HS in 10 and reduced hippocampal volume in 12. In contrast, follow‐up of 116 children without acute hyperintensity showed abnormal T2 signal in only 1 (following another episode of FSE). Furthermore, compared to controls with simple febrile seizures, FSE subjects with normal acute MRI had abnormally low right to left hippocampal volume ratios, smaller hippocampi initially, and reduced hippocampal growth.
Interpretation
Hippocampal T2 hyperintensity after FSE represents acute injury often evolving to a radiological appearance of HS after 1 year. Furthermore, impaired growth of normal‐appearing hippocampi after FSE suggests subtle injury even in the absence of T2 hyperintensity. Longer follow‐up is needed to determine the relationship of these findings to TLE. ANN NEUROL 2014;75:178–185
Abstract Background and aims Previous experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction ...and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis. Methods 4- to 6-week old male C57Bl/6 apolipoprotein E knockout ( ApoE −/− ) mice were fed a Western diet for 10 weeks and developed plaques in their brachiocephalic arteries. Results Glycocalyx coverage and thickness were significantly reduced over the plaque region compared to the non-plaque region (coverage plaque: 71 ± 23%, non-plaque: 97 ± 3%, p = 0.02; thickness plaque: 0.85 ± 0.15 μm, non-plaque: 1.2 ± 0.21 μm, p = 0.006). Values in the non-plaque region were not different from those found in wild type mice fed a normal diet (coverage WT: 92 ± 3%, p = 0.7 vs . non-plaque ApoE −/− , thickness WT: 1.1 ± 0.06 μm, p = 0.2 vs. non-plaque ApoE −/− ). Endothelial cell apoptosis was significantly increased in ApoE −/− mice compared to wild type mice ( ApoE −/− :64.3 ± 33.0, WT: 1.1 ± 0.5 TUNEL-pos/cm, p = 2 × 10−7 ). The number of apoptotic endothelial cells per unit length was 2 times higher in the plaque region than in the non-plaque region of the same vessel ( p = 3 × 10−5 ). Increased expression of matrix metalloproteinase 9 co-localized with glycocalyx shedding and plaque buildup. Conclusions Our results suggest that, in concert with endothelial apoptosis that increases lipid permeability, glycocalyx shedding initiated by inflammation facilitates monocyte adhesion and macrophage infiltration that promote lipid retention and the development of atherosclerotic plaques.
Objective: Spasticity following spinal cord injury (SCI) can impair function and affect quality of life. This study compared the effects of transcutaneous electrical nerve stimulation (TENS) and ...functional electrical stimulation (FES) on lower limb spasticity in patients with SCI.
Design: Double blind randomized crossover design.
Setting: Neuro-rehabilitation unit, Manipal University, India.
Participants: Ten participants (age: 39 ± 13.6 years, C1-T11, 1-26 months post SCI) with lower limb spasticity were enrolled in this study.
Interventions: Participants were administered electrical stimulation with TENS and FES (duration - 30 minutes) in a cross over manner separated by 24 hours.
Outcome Measures: Spasticity was measured using modified Ashworth scale (MAS) for hip abductors, knee extensors and ankle plantar flexors and spinal cord assessment tool for spastic reflexes (SCATS). Assessments were performed at baseline, immediately, 1 hour, 4 hours, and 24 hours post intervention.
Results: A between group analysis did not show statistically significant differences between FES and TENS (P > 0.05). In the within group analyses, TENS and FES significantly reduced spasticity up to 4 hours in hip adductors and knee extensors (P < 0.01). SCATS values showed significant reductions at 1 hour (P = 0.01) following TENS and 4 hours following FES (P = 0.01).
Conclusion: A single session of electrical stimulation with FES and TENS appears to have similar anti-spasticity effects that last for 4 hours. The findings of this preliminary study suggest that both TENS and FES have the potential to be used as therapeutic adjuncts to relieve spasticity in the clinic. In addition, FES may have better effects on patients presenting with spastic reflexes.
Strong enhancement of molecular circular dichroism (CD) has the potential to enable efficient asymmetric photolysis, a method of chiral separation that has conventionally been impeded by insufficient ...yield and low enantiomeric excess. Here, we study experimentally how predicted enhancements in optical chirality density near resonant silicon nanodisks boost CD. We use fluorescence-detected circular dichroism (FDCD) spectroscopy to measure indirectly the differential absorption of circularly polarized light by a monolayer of optically active molecules functionalized to silicon nanodisk arrays. Importantly, the molecules and nanodisk antennas have spectrally coincident resonances, and our fluorescence technique allows us to deconvolute absorption in the nanodisks from the molecules. We find that enhanced FDCD signals depend on nanophotonic resonances, in good agreement with simulated differential absorption and optical chirality density, while no signal is detected from molecules adsorbed on featureless silicon surfaces. These results verify the potential of nanophotonic platforms to be used for asymmetric photolysis with lower energy requirements.
(1) To determine the effect of transcutaneous electrical nerve stimulation (TENS) on poststroke spasticity. (2) To determine the effect of different parameters (intensity, frequency, duration) of ...TENS on spasticity reduction in adults with stroke. (3) To determine the influence of time since stroke on the effectiveness of TENS on spasticity.
PubMed, PEDro, CINAHL, Web of Science, CENTRAL, and EMBASE databases were searched from inception to March 2017.
Randomized controlled trial (RCT), quasi-RCT, and non-RCT were included if (1) they evaluated the effects of TENS for the management of spasticity in participants with acute or subacute or chronic stroke using clinical and neurophysiological tools; and (2) TENS was delivered either alone or as an adjunct to other treatments.
Two authors independently screened and extracted data from 15 of the 829 studies retrieved through the search using a pilot tested pro forma. Disagreements were resolved through discussion with other authors. Quality of studies was assessed using Cochrane risk of bias criteria.
Meta-analysis was performed using a random-effects model that showed (1) TENS along with other physical therapy treatments was more effective in reducing spasticity in the lower limbs compared to placebo TENS (SMD -0.64; 95% confidence interval 95% CI, -0.98 to -0.31; P=.0001; I
=17%); and (2) TENS, when administered along with other physical therapy treatments, was effective in reducing spasticity when compared to other physical therapy interventions alone (SMD -0.83; 95% CI, -1.51 to -0.15; P=.02; I
=27%). There were limited studies to evaluate the effectiveness of TENS for upper limb spasticity.
There is strong evidence that TENS as an adjunct is effective in reducing lower limb spasticity when applied for more than 30 minutes over nerve or muscle belly in chronic stroke survivors (review protocol registered at PROSPERO: CRD42015020151).
Background and Purpose
Fatigue following neurological conditions negatively impacts daily activities, reducing overall quality of life. Transcranial direct current stimulation (tDCS) for fatigue ...management is still underexplored. This scoping review explores its use in managing fatigue among various neurological conditions.
Methods
A thorough literature search was carried out using PubMed, Scopus, CINAHL, Web of Science, Embase, ProQuest, and the Cochrane Library. Google Scholar and clinicaltrials.gov were manually searched for gray literature and ongoing trials, respectively. Regardless of the study design, all studies utilizing tDCS for the management of fatigue in various neurological conditions were considered. Two reviewers independently screened all the studies, following which the data were retrieved.
Results
Studies employing tDCS for fatigue management across neurological conditions is as follows: Multiple sclerosis (MS) (n = 28, 66%), stroke (n = 5, 12%), Parkinson's disease (PD) (n = 4, 10%), post‐polio syndrome (PPS) (n = 2, 5%), traumatic brain injury (TBI) (n = 2, 5%), and amyotrophic lateral sclerosis (n = 1, 2%). All the studies used anodal stimulation, with the common stimulation site being the left dorsolateral prefrontal cortex for MS, stroke, and PD. A stimulation intensity of 1.0–4.0 mA with a duration ranging from 15 to 30 min in 1 to 24 sessions were commonly reported. The Fatigue Severity Scale (n = 21) and Modified Fatigue Impact Scale (n = 17) were frequently implemented outcome measures. Regardless of the study design, 36/42 (85.7%) studies reported an improvement in fatigue scores in the tDCS group. The common adverse events noted were tingling (n = 8, 35%), headache (n = 6, 26%), and itching (n = 6, 26%).
Discussion
Application of tDCS for fatigue was explored in individuals with stroke, PD, PPS, and TBI after MS. Even though a wide range of treatment parameters and outcome measures were adopted to assess and target fatigue, tDCS proves to have a promising role in alleviating this symptom.
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